Capillary electrophoresis as a versatile tool for quality control and epidermis permeation studies of transdermal formulations

Abstract

Capillary electrophoresis has been investigated to evaluate the performances of new transdermal formulations containing antiemetics. After optimization of the background electrolyte (sodium phosphate buffer (pH 2.5; 60 mM) containing 12% of ethanol (v/v)), domperidone, diphenhydramine, haloperidol, metoclopramide and promethazine were base-line resolved in 10 min. After hydrodynamic injection of the sample (0.5 psi for 7 s), the method was fully validated through the build of the accuracy profile. Trueness values ranged from −1.85 and 5.43% and relative standard deviation of intra-day and inter-day precision was lower than 6.20%. This method was found convenient for quality control of extemporaneous ready-to-use transdermal formulations with recoveries ranging from 91.2–107.8%. However, using hydrodynamic injection, limits of quantitation in the 0.3–2.6 μg.mL−1 range, were not low enough to evaluate the permeation rate of antimetics through epidermis. Field amplified sample injection was used to improve both sensitivity and quantitation thresholds. Several parameters (nature and concentration of the protonation agent, composition of the injected solvent, applied voltage and duration of the injection) have been optimized using a multivariate approach. In the optimized conditions, signal-to-noise ratios were improved by a 600- to 2000-fold factor, regarding the antiemetic. However, the presence of salts in the simulated body fluid solution, used as receptor medium to perform permeation kinetic study, was improper to allow the stacking effect. Therefore, a liquid-liquid extraction has been developed and applied on simulated body fluid solution. Finally, this new method has been shown strongly useful to evaluate the permeation kinetic of metoclopramide through pig epidermis.